Targeting host lipid flows: Exploring new antiviral and antibiotic strategies

Abstract

Bacteria and viruses pose serious challenges for humans because they evolve continuously. Despite ongoing efforts, antiviral drugs to treat many of the most troubling viruses have not been approved yet. The recent launch of new antimicrobials is generating hope as more and more pathogens around the world become resistant to available drugs. But extra effort is still needed. One of the current strategies for antiviral and antibiotic drug development is the search for host cellular pathways used by many different pathogens. For example, many viruses and bacteria alter lipid synthesis and transport to build their own organelles inside infected cells. The characterization of these interactions will be fundamental to identify new targets for antiviral and antibiotic drug development. This review discusses how viruses and bacteria subvert cell machineries for lipid synthesis and transport and summarises the most promising compounds that interfere with these pathways.

Statins: Could an old friend help in the fight against COVID‐19?

“…In the viral context, viruses could subvert cholesterol homoeostasis generating a protective membrane environment that facilitates virus assembly and proliferation (Deng, Almsherqi, Ng, & Kohlwein, 2010). Therefore, some authors propose targeting host cell lipid flux as a potential new antibacterial and antiviral strategy (Fernandez‐Oliva, Ortega‐Gonzalez, & Risco, 2019). Accordingly, the use of methyl‐β‐cyclodextrin for cholesterol depletion and lipid raft disruption decreased the infectivity of several viruses, such as HCV or bovine parainfluenza virus, mainly through blocking virus entry into host cells (Fernandez‐Oliva et al, 2019).…”

“…Therefore, some authors propose targeting host cell lipid flux as a potential new antibacterial and antiviral strategy (Fernandez‐Oliva, Ortega‐Gonzalez, & Risco, 2019). Accordingly, the use of methyl‐β‐cyclodextrin for cholesterol depletion and lipid raft disruption decreased the infectivity of several viruses, such as HCV or bovine parainfluenza virus, mainly through blocking virus entry into host cells (Fernandez‐Oliva et al, 2019). Similar results were observed using gemfibrozil as a lipid‐lowering drug (Bajimaya et al, 2017).…”

Active cholesterol 20 years on

“…Even though it is not one of their constituents, pathogenesis by some intracellular bacteria requires cellular cholesterol. Both innate cellular defenses and therapeutic remedies exploit this sterol dependence to combat such infections 63 . It was shown recently that cells reduce their susceptibility to certain bacteria and toxins by downregulating active plasma membrane cholesterol 64,65 …”

Obesity, Diabetes and COVID-19: An Infectious Disease Spreading From the East Collides With the Consequences of an Unhealthy Western Lifestyle

“…Inflammatory cytokines stimulate the formation of 25-HC, which in turn, promotes adipose tissue inflammation that is found in diabetes and obesity (121). The targeting of cholesterol and lipid metabolism and distribution has been proposed as a novel strategy for treating viral infections (122). The need for clustering of ACE2 and TMPRSS2 within organized domains in lipid rafts for viral entry could help explain some of the seemingly discrepant reports that increased ACE2 could facilitate infection, as described above, or actually protect against infection (123).…”